Citations

The influence of pharmacotherapy regimens on surgical patient outcomes is increasingly appreciated in the era of enhanced recovery protocols and institutional focus on reducing postoperative complications. Specifics related to medication selection, dosing, frequency of administration, and duration of therapy are evolving to optimize pharmacotherapeutic regimens for many enhanced recovery protocolized elements. This review provides a summary of recent pharmacotherapeutic strategies, including those configured within electronic health record (EHR) applications and functionalities, that are associated with the minimization of the frequency and severity of postoperative complications (POCs), shortened hospital length of stay (LOS), reduced readmission rates, and cost or revenue impacts. Further, it will highlight preventive pharmacotherapy regimens that are correlated with improved patient preparation, especially those related to surgical site infection (SSI), venous thromboembolism (VTE), nausea and vomiting (PONV), postoperative ileus (POI), and emergence delirium (PoD) as well as less commonly encountered POCs such as acute kidney injury (AKI) and atrial fibrillation (AF). The importance of interprofessional collaboration in all periprocedural phases, focusing on medication management through shared responsibilities for drug therapy outcomes, will be emphasized. Finally, examples of collaborative care through shared mental models of drug stewardship and non-medical practice agreements to improve operative throughput, reduce operative stress, and increase patient satisfaction are illustrated.

AbstractHow to deliver best care in various clinical settings remains a vexing problem. All pertinent healthcare-related questions have not, cannot, and will not be addressable with costly time- and resource-consuming controlled clinical trials. At present, evidence-based guidelines can address only a small fraction of the types of care that clinicians deliver. Furthermore, underserved areas rarely can access state-of-the-art evidence-based guidelines in real-time, and often lack the wherewithal to implement advanced guidelines. Care providers in such settings frequently do not have sufficient training to undertake advanced guideline implementation. Nevertheless, in advanced modern healthcare delivery environments, use of eActions (validated clinical decision support systems) could help overcome the cognitive limitations of overburdened clinicians. Widespread use of eActions will require surmounting current healthcare technical and cultural barriers and installing clinical evidence/data curation systems. The authors expect that increased numbers of evidence-based guidelines will result from future comparative effectiveness clinical research carried out during routine healthcare delivery within learning healthcare systems.

BackgroundPatients with high‐risk prostate cancer (HRPC) have multiple accepted treatment options. Because there is no overall survival benefit of one option over another, appropriate treatment must consider patient life expectancy, quality of life, and cost.MethodsThe authors compared quality‐adjusted life years (QALYs) and cost effectiveness among treatment options for HRPC using a Markov model with three treatment arms: (1) external‐beam radiotherapy (EBRT) delivered with 20 fractions, (2) EBRT with 23 fractions followed by low‐dose‐rate (LDR) brachytherapy boost, or (3) radical prostatectomy alone. An exploratory analysis considered a simultaneous integrated boost according to the FLAME trial (ClinicalTrials.gov identifier NCT01168479).ResultsTreatment strategies were compared using the incremental cost‐effectiveness ratio (ICER). EBRT with LDR brachytherapy boost was a cost‐effective strategy (ICER, $20,929 per QALY gained). These results were most sensitive to variations in the biochemical failure rate. However, the results still demonstrated cost effectiveness for the brachytherapy boost paradigm, regardless of any tested parameter ranges. Probabilistic sensitivity analysis demonstrated that EBRT with LDR brachytherapy was favored in 52% of 100,000 Monte Carlo iterations. In an exploratory analysis, EBRT with a simultaneous integrated boost was also a cost‐effective strategy, resulting in an ICER of $62,607 per QALY gained; however, it was not cost effective compared with EBRT plus LDR brachytherapy boost.ConclusionsEBRT with LDR brachytherapy boost may be a cost‐effective treatment strategy compared with EBRT alone and radical prostatectomy for HRPC, demonstrating high‐value care. The current analysis suggests that a reduction in biochemical failure alone can result in cost‐effective care, despite no change in overall survival.

Importance In patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited. Objective To report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial. Design, Setting, and Participants SURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021. Intervention Patients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis. Main Outcomes and Measures The prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years. Results A total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P < .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm 2 vs 1.8 [0.6] cm 2 ; P < .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P < .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention. Conclusions and Relevance Among intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.

Summary Background Previous studies suggested increased mortality in patients with hepatorenal syndrome type 1 (HRS1) and advanced acute‐on‐chronic liver failure (ACLF). Aim To assess mortality and respiratory failure (RF) in patients with HRS1 and ACLF treated with terlipressin. Methods In the CONFIRM study, we randomised 299 patients with HRS1 2:1 to terlipressin or placebo, both with albumin. At enrolment, all patients were assessed for organ failure (OF) using a validated ACLF grading system. Post hoc analyses assessed the effects of terlipressin vs. placebo on the incidence of RF and 90‐day mortality. Results The incidence of RF with terlipressin ( n = 200) was 9.4% in patients with grades 1–2 ACLF, and 30% with grade 3 ACLF ( p = 0.0002); no such difference was observed in placebo‐treated patients ( n = 99) (6.2% grades 1–2 vs. 0% grade 3 ACLF, p > 0.05). RF incidence between terlipressin and placebo in patients with grade 3 ACLF was significant ( p = 0.01). Baseline predictors of RF with terlipressin were INR ( p = 0.011), mean arterial pressure ( p = 0.037), and SpO 2 ( p = 0.014). Prior albumin as a continuous variable was not a predictor of RF. 90‐day survival between terlipressin and placebo arms was similar for grades 1–2 ACLF (55.5% and 56.6%, respectively), but lower for grade 3 ACLF (27.55% vs. 50.0%) ( p = 0.122), mainly related to RF. Conclusion Terlipressin should be used with caution in patients with HRS1 and grade 3 ACLF. Patients with hypoxaemia are at increased risk of RF and mortality.

AbstractBackgroundIn proton therapy dose calculation, Monte Carlo (MC) simulations are superior in accuracy but more time consuming, compared to analytical calculations. Graphic processing units (GPUs) are effective in accelerating MC simulations but may suffer thread divergence and racing condition in GPU threads that degrades the computing performance due to the generation of secondary particles during nuclear reactions.PurposeA novel concept of virtual particle (VP) MC (VPMC) is proposed to avoid simulating secondary particles in GPU‐accelerated proton MC dose calculation and take full advantage of the computing power of GPU.MethodsNeutrons and gamma rays were ignored as escaping from the human body; doses of electrons, heavy ions, and nuclear fragments were locally deposited; the tracks of deuterons were converted into tracks of protons. These particles, together with primary and secondary protons, are considered to be the realistic particles. Histories of primary and secondary protons were replaced by histories of multiple VPs. Each VP corresponded to one proton (either primary or secondary). A continuous‐slowing‐down‐approximation model, an ionization model, and a large angle scattering event model corresponding to nuclear interactions were developed for VPs by generating probability distribution functions (PDFs) based on simulation results of realistic particles using MCsquare. For efficient calculations, these PDFs were stored in the Compute Unified Device Architecture textures. VPMC was benchmarked with TOPAS and MCsquare in phantoms and with MCsquare in 13 representative patient geometries. Comparisons between the VPMC calculated dose and dose measured in water during patient‐specific quality assurance (PSQA) of the selected 13 patients were also carried out. Gamma analysis was used to compare the doses derived from different methods and calculation efficiencies were also compared.ResultsIntegrated depth dose and lateral dose profiles in both homogeneous and inhomogeneous phantoms all matched well among VPMC, TOPAS, and MCsquare calculations. The 3D–3D gamma passing rates with a criterion of 2%/2 mm and a threshold of 10% was 98.49% between MCsquare and TOPAS and 98.31% between VPMC and TOPAS in homogeneous phantoms, and 99.18% between MCsquare and TOPAS and 98.49% between VPMC and TOPAS in inhomogeneous phantoms, respectively. In patient geometries, the 3D–3D gamma passing rates with 2%/2 mm/10% between dose distributions from VPMC and MCsquare were 98.56 ± 1.09% in patient geometries. The 2D–3D gamma analysis with 3%/2 mm/10% between the VPMC calculated dose distributions and the 2D measured planar dose distributions during PSQA was 98.91 ± 0.88%. VPMC calculation was highly efficient and took 2.84 ± 2.44 s to finish for the selected 13 patients running on four NVIDIA Ampere GPUs in patient geometries.ConclusionVPMC was found to achieve high accuracy and efficiency in proton therapy dose calculation.

Differentiated thyroid carcinomas is associated with an excellent prognosis. The treatment of choice for differentiated thyroid carcinoma is surgery, followed by radioactive iodine ablation (iodine-131) in select patients and thyroxine therapy in most patients. Surgery is also the main treatment for medullary thyroid carcinoma, and kinase inhibitors may be appropriate for select patients with recurrent or persistent disease that is not resectable. Anaplastic thyroid carcinoma is almost uniformly lethal, and iodine-131 imaging and radioactive iodine cannot be used. When systemic therapy is indicated, targeted therapy options are preferred. This article describes NCCN recommendations regarding management of medullary thyroid carcinoma and anaplastic thyroid carcinoma, and surgical management of differentiated thyroid carcinoma (papillary, follicular, Hürthle cell carcinoma).

Abstract With aging, somatic mutations in hematopoietic stem and progenitor cells (HSPC) can give rise to clonal hematopoiesis of indeterminate potential (CHIP), a premalignant state associated with diverse age-related diseases. Here we report the largest multi-ancestry genome-wide analysis of CHIP to date (N = 1,018,305), including individuals of African (N = 85,978), Admixed American (N = 191,371), East Asian (N = 13,532), European (N = 694,015), and South Asian (N = 13,193) ancestry. Multi-ancestry meta-analyses identified 72 genome-wide significant loci, including 44 novel associations implicating genes such as AFF1 , ATF7IP , ATP8B4 , BCL2 , CEBPA , CYRIA , DNM2 , ELF1 , NKX2-3 , PIK3CB , PRDM16 , RPN1 , TERC , and TRIM4 . Notably, variants at MECOM and PHF20L1 showed opposite allelic effects between DNMT3A - and non- DNMT3A -driven CHIP, highlighting driver-specific germline influences. Implicated loci converge on pathways regulating telomere maintenance, cell-cycle control, hematopoietic transcription, DNA damage response and immune signaling. These findings support a model in which germline variation both expands the HSPC pool and biases clonal selection in a driver-dependent manner, providing a mechanistic basis for inter-individual heterogeneity in CHIP. Phenome-wide association analyses further linked CHIP to hematologic, neoplastic, and circulatory traits, with enrichment across hematopoietic and non-hematopoietic cell types. Together, this work expands the genomic and phenomic landscape of CHIP and reveals germline–somatic interactions that shape clonal evolution during aging.